For someone who didn't intend to wreck Sol system's fragile balance of power, Jim Holden did a pretty good job of it.

While Earth and Mars have stopped shooting each other, the core alliance is shattered. The outer planets and the Belt are uncertain in their new - possibly temporary - autonomy.

Then, on one of Jupiter's moons, a single super-soldier attacks, slaughtering soldiers of Earth and Mars indiscriminately and reigniting the war. The race is on to discover whether this is the vanguard of an alien army, or if the danger lies closer to home.

Martian marine Roberta “Bobbie” Draper the UN troops were fleeing from someone infected with protomolecule. Shooting the monster doesn't seem to damage it, and it proceeds to rip the marines apart with its bare hands. It's just about to kill Bobbie when it grows another arm, then promptly explodes in a ball of fire. Bobbie wakes up days later in a hospital. Her superiors don't believe her story about the monster until they watch the video from her gun cam.

Space battles around Ganymede between the UNN and the MCRN causes one of the gigantic orbital mirrors, used to direct sunlight to crops, to crash into the moon, destroying the lab where Praxidike Meng, botanical engineer, worked.
He evacuates and goes to daycare to retrieve his daughter Mei, only to find she's been taken by a lady the computer system mistook for her mother, a suspicioous case of fraud and kidnapping. At this point, it is not apparent that Dr. Strickland is involved so there's immense fear of tragedy from lack of proper medical attention. Prax searches everyday amongst all the casualties for his daughter, but she never turns up.

Basia Merton, whose youngest son Katoa is also missing, leaves without that son. Although, this is not without a physical confrontation between the two distraught fathers. There's an exchange which Basia's eldest child, his young daughter Felcia, intercedes and terminates. Basia takes passage with his remaining family aboard Barbapiccola

Holden and the crew of the Rocinante (Naomi, Amos, and Alex) are doing mundane work for Fred Johnson, hunting down space pirates, when Fred calls them back because of the Ganymede situation. They take an inconspicuous ship, the Somnambulist, to Ganymede to check out the situation.

Chrisjen Avasarala, assistant to the Undersecretary of Executive Administration on Earth, is trying to stave off the coming war between Earth and Mars. She notices there's a spike in activity around Venus, where the protomolecule-infected Eros station crashed after the Eros incident, during the Ganymede attack; she interviews Jules-Pierre Mao, thinking perhaps the infected Julie might have contacted him from Venus. He won't admit to anything, but she thinks he knows much more than he's letting on. She also gets intelligence reports saying Holden is on Ganymede, and that Admiral Nguyễn has secretly been deploying Earth ships there as well. She pulls some strings and pulls all the ships back, averting war.

Prax gives up his food to a hacker in exchange for videos from Mei's daycare. He finds the videos of the mystery woman and the doctor, but the hacker leverages Prax's desperation to extort more and won't show him more unless Prax gets him additional chicken. Prax recognizes Holden from his previous broadcasts, and asks Holden to help him find Mei. The hacker gets Prax the videos he wants after they bring him a case of chicken and Amos roughs him up. The videos show Mei's abductors taking her into an old, unused corridor just before the attacks started.

On the way to the abandoned corridor, they encounter a stay-behind network of Pinkwater security operatives in MCRN armor, but Holden proposes to get them off Ganymede if they join forces, and they accept the deal. They breach the corridor and find a lab; inside they find the body of Basia's son, who has apparently been infected with the protomolecule. In the next room over, they encounter a room full of armed people having a pizza party; Holden tries to be politic, but Prax goes off half-cocked about his daughter and takes out his gun, causing a firefight to immediately break out. Holden's squad is much quicker and manage to shoot everyone first.

They encounter more resistance the farther into the complex they go, and many of the Pinkwater people are killed; it seems the unknown players were evacuating through a secret docking port, while simultaneously fighting against an unknown third party. In the lab equipment wreckage they find fine, black filaments. Holden is horrified and calls for immediate withdrawal and extraction.

Just outside their ship, they're captured by a UN security force sent by Avasarala, but manage to escape; however, Ganymede is then attacked by nukes and/or gauss rounds. They try to backtrack to the secret landing pad, but find it blocked from all the damage, and are forced to go outside the dome in the vacuum of space. Alex comes in hot in the Roci and they manage to escape after avoiding torpedoes fired from seemingly all the ships in orbit.

Avasarala's immediate superior, Sadavir Errinwright (UN Undersecretary of Executive Administration), puts her on the Venus project and gives her a blank check. She quickly realizes this is merely politicking to get her off the Mars conflict, presumably by Adm. Nguyễn, since he somehow got even more ships to send to Ganymede.

Avasarala hires Bobbie to help her look into Venus, and hands over all her intel. An hour before the fighting on Ganymede, the warship Arboghast around Venus is blown up – stripped apart in layers and disassembled.

On the Roci, they find that during their escape, a monster pulled open the cargo bay door with its bare hands and has been stowing away in there, in the vacuum, for days. Holden and Amos try to attack it, but it attacks them; it flings a mag-locked pallet at Holden and traps him there. They shoot it a few times and it goes back to hibernating. Prax notices that the protomolecule seems to be constrained to its host, instead of reallocating its bits around like on Eros, and that it's feeding off a radiation leak in the corner. Prax goes EVA and throws radioactive bait past the monster; it follows after the bait out into space, but leaves a bomb in the cargo bay. Alex does a full burn with the Roci’, killing the monster; however, this causes the bomb in the cargo bay to go off, sending the ship into a spin and killing the reactor and thrusters.

Bobbie notices Avasarala's assistant, Soren, taking a data chip somewhere he shouldn't be going, so she follows him to a bar. He gives the data to someone militaristic looking, clearly disguised as a civilian. Soren tries to exculpate himself by telling Avasarala that Bobbie is actually a Martian Intelligence operative, but she instantly realizes he is lying. Avasarala is not surprised when Bobbie reveals the truth and understands the connection that Soren was leaking/withholding info for Nguyễn. She further deduces that Errinwright must be responsible for the monster(s) on Ganymede, working with Mao-Kwikowski to weaponize the protomolecule. She calls to question Errinwright, and he realizes that she made the connection, so he tells her she'll soon be flying to Ganymede on a Mao-Kwik yacht. She has no choice but to acquiesce, otherwise she'll lose her political power. Chrisjen Avasarala tells Bobbie she's the only remaining fully trustworthy person in her team and tells her she's coming along.

Bobbie and Avasarala get on Mao's yacht, the Guanshiyin. Mao is supposed to be going along too, but he abruptly excuses himself at which point Avasarala realizes she is compromised and to a great extent trapped and shackled.

The Roci arrives at Tycho. Naomi, who has been fed up with Holden acting like Detective Miller, heatedly leaves him and the ship. Holden demands Fred tell him if he was involved with Ganymede; Fred fires him for his constant insubordination and tells him "no" on the way out. Surprisingly, Holden feels like a weight has been lifted off his chest now that he's free to take whatever jobs he wants.

Prax tries to raise money to search for Mei but can't afford to hire anyone; Amos is taken aback and assures him they're already going to do it. Holden broadcast a message about Mei's situation, Dr. Strickland, and the protomolecule. Within hours, the plea garners hundreds of thousands in donations. Holden apologizes to Naomi and she accepts to rejoin the crew, but their relationship status still separated. Prax gets a message from, Dr Moynahan, a former colleague of Strickland who reveals "Strickland" is merely an alias of the man he recognizes as Carlos Merrian. He was a former peer at CMTU biosciences lab, on biological development constraint systems, but Merrian quit over ethical differences choosing to work for Protogen.

Prax puts observations and data together to hypothesize that Strickland (or Merrian) abducted Mei because of her compromised immune system, since it wouldn't fight back against the protomolecule, the way the previous monsters have; they've been engineered with a bomb as a failsafe, so if they get out of control they can be destroyed; however, the protomolecule eventually adapts and ejects the bomb.

They realize that there must have been two monsters on Ganymede: the one they accidentally let out when they stormed the lab, and another that was presumably let loose just to see what would happen. Prax reasons that the monsters must have been shipped in from somewhere close, otherwise they would've adapted and ejected their bombs. He follows the money trail through tariff records and concludes they must be on Jupiter's moon, Io.

Inexplicably, Prax starts getting death threats instead of donations; his ex-wife Nicola is seen in a broadcast making a statement which impugns Prax with allegations of spousal assault and of abusing Mei. Avasarala becomes alerted to the message and concludes that Errinwright's cabal compelled Nicola in order to stop Holden's growing threat, suggesting he's getting too close to the truth. She gets more intel about Venus, and her consultant, Michael-Jon de Uturbé, thinks that the spikes look like neuronal(?) synapses, implying that it is sentient. Admiral Souther contacts her and says Nguyễn sent six destroyers after Holden; she wants to send a message out to warn him, but Mao's crew blocks her with claims of radio access errors. Thus demonstrating that she's being held captive, Avasarala declares authority to commandeer the ship. Bobbie puts on her mechanized combat armor and fights her way to the bridge. The captain surrenders, but the yacht is too slow to make it to Holden in time. Luckily, the Razorback racing pinnace is on board.

Holden gathers the crew together to figure out who they are as a group unit and what they want to do in the future. They take a vote and decide to keep him the captain; Holden says they're going to incorporate, and each of them will own part of the Roci. Naomi is glad to see the old Holden back.

Avasarala tells Holden to meet her, and comes aboard; she explains the dire situation they're in. They produce a video explaining she's there on behalf of the UN to meet with Holden and a Mars representative (Bobbie) as a multilateral investigation of Ganymede. She also denounces media exploitation of Prax's mentally ill ex-wife. In so doing, she exonerates Prax. She shows the Roci crew Bobbie's suit video, which reaffirms Prax's hypothesis about the protomolecule ejecting its failsafe. She shows them the Venus data and Prax further realizes that Venus is communicating with the monsters in real time – one learns what the other learns.

Avasarala puts all this info into a video and sends it to Errinwright; however, instead of pulling back, he sends the warships toward them even faster. Avasarala sends the info to Admirals Souther and Leniki, who she trusts. Bobbie suggests they make a plea to the Martians for backup; Avasarala tells them she's being attacked by a rogue element of the UN Navy while on a peacekeeping mission to Jupiter, and to requires their help.

The Martian cruiser fires torpedoes first, and when the UN ships turn to fire at Martians, Bobbie fires the torpedoes that take out the first UN ship, turning the tide of battle in their favor. Some torpedoes were fired at the Roci, but PDCs took them out; however, three stray PDC shots go through Prax's quarters and need repairs. The MCRN ships resupply them, and Holden gets Bobbie an arm cannon for her suit with incendiary rounds.

Avasarala tells the Secretary-General, Esteban Sorrento-Gillis, what the situation is; he forms an investigative committee. After he subsequently is forced to condemn Nguyễn's actions she concludes Errinwright has struck a bargain exposing the admiral but is finished. The Secretary-General himself must have also effectively lost all political influence and become a lame duck until someone else takes the office.

Bobbie studies her armor-cam video repeatedly to develop a combat strategy; she determines that the monster's failsafe might kick in when it receives too much damage, and that it's only good at attacking straight on.

Admiral Souther joins his fleet with the Martian and they head to Io. Nguyễn has dozens of ships in orbit, making this the largest fleet action in history. From aboard the UNN Agatha King, Nguyễn threatens to send protomolecule weapons at Mars; Mars threatens to glass the moon in return. The Secretary-General recalls Nguyễn to Earth. Nguyễn launches hundreds of protomolecule monsters from the surface of Io, targeting Mars, then tries to fastburn away. The monster transports cut thrust entering ballistic trajectory and Nguyễn shuts off their transponders, so they can't be tracked. One of the monster makes it onto the King, and Nguyễn immediately surrenders, but Avasarala says there's no way in hell anyone is going on that ship. Even though he's a dead man walking, Nguyễn refuses to turn the transponders back on, so no one knows how many monsters made it past the fleet to Mars. Holden sends Bobbie, Amos, and Prax down to Io; he's going over to the King to turn transponders on.

The monster breached the reactor on the King, so Holden has to wear a radiation suit instead of proper armor. He takes the Razorback to Agatha King and is attacked by a UN sailor, Larson, hiding in a storage locker; luckily, he thinks Holden's an admiral and helps him get to the CIC (Combat Information Center). The infected are all congregated in the galley, and they're all the new version of the vomit zombies with the glowing blue eyes. They run through and just barely make it up the elevator to the CIC, where they find Nguyễn still alive. He still won't give up the transponder codes, so Holden shoots him in the throat, mid-sentence. Having reactivated the transponders, he find the ships's self destruct button, but there's no timer. Since his suit was ripped while running from the "vomit zombies", Larson agrees to remain behind to trigger the sequence. Holden leaves out an airlock and after allowing enough time, Larson blows the Agatha King, Admiral Augustus Nguyễn's ship.

Io is tectonically unstable and highly radioactive. Amos and Prax go into the base while Bobbie stays outside to fight one of the monsters. Her incendiary rounds stop it from healing itself, but don't take it out. She adopts a tactic of evasion at 90° perpendicular fallback vectors, and her theory about the monsters not being good at corners is effective. The monster can't catch her, so it starts tearing up big chunks of rocks and throwing them at her. She continues to dodge and shoot, but instead of the bomb going off and destroying it, it rips it off and throws it at her. It goes off near her feet, sending her flying and greatly damaging her suit. The monster sidles up and pukes on her, but seems curious about why she's not becoming infected. A tube comes out of its midsection and sprays goo all over her, probing her suit for entry points. Fortunately, Bobbie's gun comes back online and she blows its head off.

Prax and Amos find Strickland accompanied with the mystery woman, who turns out to be his handler, in the lab. She tries to convince Strickland to flee with her, but he sees the writing on the wall and shoots her. Amos and Prax confront him and he says he was the one who kept the children safe, that they would've been infected without him, but they call him out on being a sociopath and Amos blows him apart with his auto shotgun. After a heartfelt reunion with Mei, they get her and the other kids back to the Roci’’, and Bobbie too.

Errinwright is "retired" and Avasarala gets his job as Undersecretary of Executive Administration. She tells Bobbie that anything she wants to do, Avasarala will make it happen. Holden tells his family to come to Luna and meet Naomi; turns out they're racist against Belters but they'll come anyway. Avasarala brings in Jules-Pierre Mao to humiliate him, while Holden unofficially observes; she tells him he's going to be locked up and forced to watch her disassemble everything he's built – the ultimate punishment for a man like him. She puts Prax in charge of rebuilding Ganymede, much to his pleasure.

Fred Johnson, in a demonstration of his nuclear capabilities, nukes the protomolecule missile monsters when they get near Tycho station. This causes Venus to violently react by shooting black filaments thousands of kilometers long, bigger than Ceres Station or Ganymede, off of the surface and into space, swatting starships out of the way like gnats.

The title refers to Caliban, one of the primary antagonists in William Shakespeare's play The Tempest[3]; just as the half-human slave Caliban revolts against his bondage in The Tempest, the human-protomolecule hybrids seek to throw off their shackles in the book[4].